The following research proposal represents a major aspect in the long-range effort of this laboratory to elucidate the mechanism of action of steroid hormones. It is concerned with (1) the interaction of the progesterone receptor with nucleotides, ATP in particular, and (2) the possible role of nucleotides in some aspects of receptor function. Over the past two years, we have obtained considerable evidence for an interaction of the avian progesterone receptor with ATP. The binding of receptor to ATP has been shown using ATP-Sepharose affinity chromatography. This binding is reversible and shows a preference for ATP. These results indicate a possible role of ATP in receptor function and efforts are being made to identify such a function. Very recent studies show that: (1) ATP can modify the in vitro activation of progesterone receptor, and (2) highly purified receptor preparations are able to metabolize ATP. The studies of this proposal are designed to firmly establish the existence and properties of the ATP-Receptor interaction and to clearly identify and describe activities of the receptor that involve nucleotide interactions.